This collaborative project aims to develop graphical user interfaces (GUIs) that allow both expert and non-expert users to easily setup, perform, and analyze various membrane simulations. These toolsets will greatly reduce the learning curve that typically prevents non-experts from utilizing simulations to study membrane systems. Based on the Membrane Builder software in CHARMM-GUI (www.charmm-gui.org/input/membrane), the project has three specific aims. In AIM 1, a cross-platform, standalone GUI toolset will be developed to perform analyses of membrane simulation trajectories from various simulation programs including CHARMM, Amber, GROMACS, and NAMD. In AIM 2, Membrane Builder will be further developed by (i) including more (biologically important) lipid molecules, (ii) developing tools to build monolayer, micelle, and vesicle systems, (iii) providing simulation inputs for GROMACS and Amber packages (Membrane Builder currently provides the inputs for CHARMM and NAMD programs). In AIM 3, Membrane Builder/Analyzer will be used to study (i) the influences of chain saturation, chain length, cholesterol concentration, and lipid head groups on lipid properties, (ii) membranes with the phosphoinositol signaling lipid, and (iii) membranes with sphingolipids and cholesterol. Such studies will also provide the lipid structural libraries as well as the equilibrated systems of these membranes to facilitate the building of mixed lipid systems in Membrane Builder. Membrane Builder/Membrane Analyzer will be hosted in the CHARMM-GUI web server.
Biological membranes and membrane-associated proteins/peptides play important roles in many cellular processes (transport of nutrients and facilitating function within the cell) and in bioengineering / biotechnology (possible vehicles for vaccines/drugs and models for solid-support lipid monolayers for technological assessment of membranes). Therefore, studying the phenomena related to lipid membranes and membrane proteins in atomic detail has been of great interest. Molecular dynamics simulations (time progression of molecules to probe their function) have been particularly useful in understanding the dynamics and the underlying energetics of membrane proteins, which is difficult to extract from experimental data alone. Thus, computational modeling and simulations of membranes and membrane proteins can supplement experiments in understanding their structure and function at the molecular/atomic level. This project seeks to foster synergistic scientific research and education by providing the Membrane Builder/Analyzer GUI resources for any general membrane or membrane protein simulations to students and researchers in a wide array of research contexts and multiple simulation communities. In particular, the team will organize a workshop to directly interact with the user community, and also develop a summer program for local high school students to provide research experience in membrane simulations using Membrane Builder/Analyzer.
